This slide reviews
some of the steps in the viral life cycle and highlights the steps targeted
by novel antiretrovirals currently in development.

Entry inhibitors
block HIV entry into CD4+ cells. Enfuvirtide is a fusion inhibitor and is the
only approved member of this entry inhibitor class. Drugs currently in
development include TNX-355, an antibody that binds to the CD4+ cell receptor
to block virus entry; CCR5 inhibitors that block binding to the CCR5
chemokine coreceptor; and CXCR4 inhibitors that block binding to the CXCR4
chemokine coreceptor.

Once a virus enters
a cell, it has to uncoat. Uncoating of the virus may involve a host protein
called cyclophilin A, for which inhibitors are being developed. Presumably,
these inhibitors block the interaction between cyclophilin A and the virus
thereby preventing uncoating.

Reverse
transcription of the viral RNA genome into double-stranded DNA is the next
step in the viral life cycle. There are currently several approved reverse
transcriptase inhibitors and these are, obviously, not considered novel
agents.

The next step is
integration of the double-stranded viral DNA into the host chromosome. This
process is accomplished via the viral integrase enzyme. Clinical data on 2
integrase inhibitors, MK-0518 and GS-9137, will be discussed later.

The viral genome is
then transcribed and translated into proteins. These viral proteins are
cleaved by proteases, including the proteases carried by the virus itself.
The process of protein cleavage followed by assembly of the virus is termed
maturation. A new drug, PA-457, inhibits this process of maturation or
assembly of the virus core without specifically interfering with protease
activity. PA-457 is not a protease inhibitor it is a maturation inhibitor.